The Potential Dual Role of H2.0-like Homeobox in the Tumorgenesis and Development of Colorectal Cancer and Its Prognostic Value.

IF 2.7 4区 医学 Q2 Medicine Canadian Journal of Gastroenterology and Hepatology Pub Date : 2023-09-09 eCollection Date: 2023-01-01 DOI:10.1155/2023/5521544
Shuo Chen, Lin Zhang, Kai Wang, Jizhen Huo, Siqi Zhang, Xipeng Zhang
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Abstract

Background: H2.0-like homeobox (HLX) is highly expressed in several hematopoietic malignancies. However, the role of HLX in the carcinogenesis and progression of colorectal cancer (CRC) patients has rarely been reported.

Methods: In this study, the data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The diagnostic value of HLX was analyzed by the R package "pROC." The overall survival was estimated using the "survival" and "survminer" packages. A nomogram was established to predict 1-, 3-, and 5-year overall survival of CRC patients. The CIBERSORT software was employed to calculate the relative proportions of 22 immune cells.

Results: HLX expression was downregulated in CRC patients. Remarkably, HLX expression was increased with stage (stage I-stage III) of CRC, and the CRC patients with high HLX expression exhibited a poor prognosis. The promoter methylation level of HLX was prominently increased in CRC samples compared to paracancerous samples. We also found that the six miRNAs target HLX genes, leading to its downregulation, and HLX expression had a negative correlation with its downstream target gene BRI3BP in both CRC and normal samples. Finally, we found that the 12 immune infiltrating cells were observably different between high and low HLX expression groups. The HLX had a significant positive correlation with 8 immune checkpoints (PD-1 (PDCD1), CTLA4, PDL-1 (CD274), PDL-2 (PDCD1LG2), CD80, CD86, LAG3, and TIGIT) expressions.

Conclusion: HLX probably played a carcinostasis role in the early stages of CRC but exhibited a cancer-promoting effect in the advanced stages. Meanwhile, HLX could serve as a reliable prognostic indicator for CRC.

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H2.0类同源异型盒在癌症发生发展中的潜在双重作用及其预后价值。
背景:H2.0样同源盒(HLX)在多种造血系统恶性肿瘤中高度表达。然而,HLX在癌症(CRC)患者的致癌和进展中的作用很少报道。方法:本研究数据来源于癌症基因组图谱和基因表达综合数据库。HLX的诊断价值通过R软件包“pROC”进行分析。总生存率通过“生存率”和“生存矿工”软件包进行估计。建立列线图来预测CRC患者的1年、3年和5年总生存率。CIBERSORT软件用于计算22个免疫细胞的相对比例。结果:CRC患者HLX表达下调。值得注意的是,HLX的表达随着CRC的分期(I-III期)而增加,并且HLX高表达的CRC患者表现出较差的预后。与癌旁样本相比,CRC样本中HLX的启动子甲基化水平显著增加。我们还发现,六种miRNA靶向HLX基因,导致其下调,并且在CRC和正常样本中,HLX的表达与其下游靶基因BRI3BP呈负相关。最后,我们发现HLX高表达组和低表达组的12个免疫浸润细胞存在显著差异。HLX与8个免疫检查点(PD-1(PDCD1)、CTLA4、PDL-1(CD274)、PDL-2(PDCD1LG2)、CD80、CD86、LAG3和TIGIT)的表达呈显著正相关。结论:HLX可能在CRC早期起到抑癌作用,但在晚期起到促癌作用。同时,HLX可作为CRC的可靠预后指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.80
自引率
0.00%
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0
审稿时长
37 weeks
期刊介绍: Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.
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